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Biomedical subjects

M Bertram

Publications and source records attributed to M Bertram.

At least 19 recordsLinked to original sources

Controlling turbulence in a surface chemical reaction by time-delay autosynchronization.

A global time-delay feedback scheme is implemented experimentally to control chemical turbulence in the catalytic CO oxidation on a Pt(110) single crystal surface. The reaction is investigated under ultrahigh vacuum conditions by means of photoemission electron microscopy. We present results showing that turbulence can be efficiently suppressed by applying time-delay autosynchronization. Hysteresis effects are found in the transition regime from turbulence to homogeneous oscillations. At optimal delay time, we find a discontinuity in the oscillation period that can be understood in terms of an analytical investigation of a phase equation with time-delay autosynchronization. The experimental results are reproduced in numerical simulations of a realistic reaction model.

Journal Article↗

Monocyte function and plasma levels of interleukin-8 in acute ischemic stroke.

Activated monocytes may contribute to the pathogenesis of ischemic stroke. We tested the hypothesis that release products and procoagulant activity of monocytes are increased in acute ischemic stroke. In patients on days 1, 3 and 7 after ischemic stroke and in age- and sex-matched healthy control subjects, we assessed plasma levels of interleukin 8 (IL-8) and neopterin (enzyme linked immunosorbent assay, ELISA) and investigated superoxidanion release (ferricytochrome C reduction), procoagulant activity (one-stage clotting assay) and tissue factor (TF) gene transcription (reverse transcriptase polymerase chain reaction) by monocytes. As compared to control subjects (n=23), IL-8 levels were increased on day 1 after stroke (n=22; p=0.005) and remained elevated on days 3 and 7. Neopterin levels were elevated on days 3 and 7 (p<0.05, respectively) but not on day 1. Neopterin and IL-8 were not correlated with monocyte counts. Superoxid anion production by stimulated and unstimulated monocytes was not different between groups. TF mRNA could neither be detected in monocytes from patients investigated within 12 h after ischemia (n=12) nor in control subjects (n=10) and procoagulant activity of cells was similar in both groups. Our results indicate increased monocyte activation after ischemic stroke although not all activation parameters were elevated. We found no support for the hypothesis that circulating monocytes express TF and possess increased procoagulant activity. Elevated IL-8 may contribute to stroke pathophysiology by activating polymorphonuclear leukocyte (PMNL) activation early after ischemia.

Acute Disease↗

Controlling chemical turbulence by global delayed feedback: pattern formation in catalytic CO oxidation on Pt(110).

Control of spatiotemporal chaos is one of the central problems of nonlinear dynamics. We report on suppression of chemical turbulence by global delayed feedback using, as an example, catalytic carbon monoxide oxidation on a platinum (110) single-crystal surface and carbon monoxide partial pressure as the controlled feedback variable. When feedback intensity was increased, spiral-wave turbulence was transformed into new intermittent chaotic regimes with cascades of reproducing and annihilating local structures on the background of uniform oscillations. The global feedback further led to the development of cluster patterns and standing waves and to the stabilization of uniform oscillations. These findings are reproduced by theoretical simulations.

Journal Article↗

Pattern formation in a surface chemical reaction with global delayed feedback.

We consider effects of global delayed feedback on anharmonic oscillations in the reaction-diffusion model of the CO oxidation reaction on a Pt(110) single-crystal surface. Depending on the feedback intensity and the delay time, we find that various spatiotemporal patterns can be induced. These patterns are characterized using a transformation to phase and amplitude variables designed for anharmonic oscillations. Typical feedback-induced patterns represent traveling phase flips, asynchronous oscillations, and dynamical clustering. Three different types of cluster patterns are identified: amplitude clusters, phase clusters, and cluster turbulence. For phase clusters, two different front instabilities are possible. A pitchfork bifurcation leads to propagation of cluster fronts. An instability of the state of phase balance results in spatial front oscillations.

Journal Article↗

Inherited Myoclonus-dystonia syndrome: narrowing the 7q21-q31 locus in German families.

Genetic studies were performed in four German families with autosomal dominant myodonus-dystonia syndrome. Mutations in the D2 dopamine receptor gene, which have been implicated in this disorder, were excluded in all four families by linkage analysis and direct sequencing. All four families supported linkage to the second reported locus on chromosome 7q21 with a combined maximum multipoint lod score of 5.99. The observation of key recombinations in one family refined the disease locus to a 7.2 cM region flanked by the markers D7S652 and D7S2480.

Adolescent↗

Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome.

The dystonias are a common clinically and genetically heterogeneous group of movement disorders. More than ten loci for inherited forms of dystonia have been mapped, but only three mutated genes have been identified so far. These are DYT1, encoding torsin A and mutant in the early-onset generalized form, GCH1 (formerly known as DYT5), encoding GTP-cyclohydrolase I and mutant in dominant dopa-responsive dystonia, and TH, encoding tyrosine hydroxylase and mutant in the recessive form of the disease. Myoclonus-dystonia syndrome (MDS; DYT11) is an autosomal dominant disorder characterized by bilateral, alcohol-sensitive myoclonic jerks involving mainly the arms and axial muscles. Dystonia, usually torticollis and/or writer's cramp, occurs in most but not all affected patients and may occasionally be the only symptom of the disease. In addition, patients often show prominent psychiatric abnormalities, including panic attacks and obsessive-compulsive behavior. In most MDS families, the disease is linked to a locus on chromosome 7q21 (refs. 11-13). Using a positional cloning approach, we have identified five different heterozygous loss-of-function mutations in the gene for epsilon-sarcoglycan (SGCE), which we mapped to a refined critical region of about 3.2 Mb. SGCE is expressed in all brain regions examined. Pedigree analysis shows a marked difference in penetrance depending on the parental origin of the disease allele. This is indicative of a maternal imprinting mechanism, which has been demonstrated in the mouse epsilon-sarcoglycan gene.

Adolescent↗

Resonant phase patterns in a reaction-diffusion system

Resonance regions similar to the Arnol'd tongues found in single oscillator frequency locking are observed in experiments using a spatially extended periodically forced Belousov-Zhabotinsky system. We identify six distinct 2:1 subharmonic resonant patterns and describe them in terms of the position-dependent phase and magnitude of the oscillations. Some experimentally observed features are also found in numerical studies of a forced Brusselator reaction-diffusion model.

Journal Article↗

Managing the therapeutic dilemma: patients with spontaneous intracerebral hemorrhage and urgent need for anticoagulation.

Physicians face a therapeutic dilemma in patients with acute hemorrhagic stroke requiring long-term, high-intensity anticoagulants because this treatment increases the risk of intracranial hemorrhage (ICH) 8- to 11-fold. We retrospectively studied 15 patients with ICH which occurred under anticoagulation with phenprocoumon, with an international norrmalized ratio (INR) of 2.5-6.5 on admission. Hemispheric, thalamic, cerebellar, intraventricular, or subarachnoid hemorrhage without aneurysm occurred. Absolute indications for anticoagulation were double, mitral, or aortic valve replacement, combined mitral valve failure with atrial fibrillation and atrial enlargement, internal carotid artery-jugular vein graft, frequently recurring deep vein thrombosis with risk of pulmonary embolism, and severe nontreatable ischemic heart disease. As soon as the diagnosis of ICH was established, INR normalization was attempted in all patients by administration of prothrombin complex, fresh frozen plasma, or vitamin K. After giving phenprocoumon antagonists (and neurosurgical therapy in four patients) heparin administration was started. Nine patients received full-dose intravenous and six low-dose subcutaneous heparin. The following observations were made: (a) All patients with effective, full-dose heparin treatment with a 1.5- to 2-fold elevation in partial thromboplastin time after normalization of the INR were discharged without complication. (b) Three of four of the patients with only incomplete correction of the INR (> 1.35) experienced relevant rebleeding within 3 days (all patients with an INR higher than 1.5), two of whom were on full-dose heparin. (c) Three of seven of the patients with normalized INR and without significant PTT elevation developed severe cerebral embolism. Although our data are based on a retrospective analysis, they support treatment with intravenous heparin (partial thromboplastin time 1.5-2 times baseline value) after normalization of the INR in patients with an ICH and an urgent need for anticoagulation.

Aged↗

Transcranial colour-coded sonography for the bedside evaluation of mass effect after stroke.

Repeated cranial computerized tomography scan examination in patients with elevated intracranial pressure is time consuming and requires patient transportation. We prospectively evaluated the diagnostic value of transcranial duplex sonography as a bedside tool for detection of the mass effect after space-occupying ischemic stroke and brain haemorrhage and for evaluating the width and dislocation of the ventricular system and the dislocation of brain mid-line structures. We used transcranial duplex sonography in 21 consecutive patients with space-occupying ischemic middle cerebral artery infarction and brain haemorrhage. The transcranial duplex sonography examinations were performed within 2 h before or after corresponding follow-up cranial computerized tomography scans. We measured the third ventricular width as a parameter for infratentorial and the mid-line shift for supratentorial space-occupying effect. In all patients, mid-line structures could be identified by transcranial duplex sonography. Significant third ventricular dilation was found subsequently in most patients with infratentorial mass effect, and mid-line shift occurred in all patients with supratentorial space-occupying lesions, respectively. The mean difference (absolute values) between transcranial duplex sonography and cranial computerized tomography measurements was 0.8 mm for the ventricular width (standard deviation 1 mm) and 1.1 mm for the mid-line shift (standard deviation: 1.46 mm), with a tendency for these parameters to be underestimated at higher values using transcranial duplex sonography. The linear correlation coefficients were R = 0.97 and R = 0.94, respectively. Transcranial duplex sonography appears to be a sufficiently reliable bedside method for evaluating the width and the lateral displacement of the third ventricle, as validated by cranial computerized tomography scan. Thus, it may be suitable for monitoring the space-occupying effect of both supra- and infratentorial strokes during treatment on critical care and stroke units.

Adult↗

Serum procalcitonin levels in bacterial and abacterial meningitis.

OBJECTIVES: To test the hypothesis that serum procalcitonin (PCT) levels are elevated in patients with bacterial meningitis and remain within normal limits in patients with abacterial meningitis. DESIGN: Prospective case series. SETTING: Tertiary care center. PATIENTS: A total of 30 patients (13 men and 17 women) with a mean age of 52 yrs, having acute bacterial (n = 16) or abacterial (n = 14) meningitis. INTERVENTIONS: Blood and cerebrospinal fluid samples. MEASUREMENTS AND MAIN RESULTS: Patients with abacterial meningitis were younger and had a shorter hospital stay. Of 16 patients with bacterial meningitis, 14 were in a septic condition at admission, but only 5 of 14 patients with abacterial meningitis were in a septic condition at admission. At discharge, 12 patients were without symptoms, 9 patients were moderately disabled, and 9 were severely disabled. No patient died. At admission, PCT, C-reactive protein, white blood cell and cerebrospinal fluid leukocyte counts, and cerebrospinal fluid protein and lactate levels were higher and the serum/cerebrospinal fluid glucose quotient was lower in patients with bacterial meningitis as compared with those with abacterial meningitis (p < .001). PCT was the variable with the highest specificity for bacterial infections (100%), but there were false-negative findings in five patients with bacterial meningitis (a sensitivity of 69%). Persistently elevated or increasing PCT levels after 2 days were associated with an unfavorable clinical course. CONCLUSIONS: Our results indicate that PCT is a useful additional variable for distinguishing bacterial from abacterial meningitis. In patients with abacterial meningitis, PCT levels do not increase even in cases of viral sepsis. Elevated PCT levels indicate a bacterial origin with high specificity, but false-negative results can occur.

Adolescent↗

Four-phase patterns in forced oscillatory systems

We investigate pattern formation in self-oscillating systems forced by an external periodic perturbation. Experimental observations and numerical studies of reaction-diffusion systems and an analysis of an amplitude equation are presented. The oscillations in each of these systems entrain to rational multiples of the perturbation frequency for certain values of the forcing frequency and amplitude. We focus on the subharmonic resonant case where the system locks at one-fourth the driving frequency, and four-phase rotating spiral patterns are observed at low forcing amplitudes. The spiral patterns are studied using an amplitude equation for periodically forced oscillating systems. The analysis predicts a bifurcation (with increasing forcing) from rotating four-phase spirals to standing two-phase patterns. This bifurcation is also found in periodically forced reaction-diffusion equations, the FitzHugh-Nagumo and Brusselator models, even far from the onset of oscillations where the amplitude equation analysis is not strictly valid. In a Belousov-Zhabotinsky chemical system periodically forced with light we also observe four-phase rotating spiral wave patterns. However, we have not observed the transition to standing two-phase patterns, possibly because with increasing light intensity the reaction kinetics become excitable rather than oscillatory.

Journal Article↗

[Spectrum of neurological symptoms in dissections of brain-supplying arteries].

BACKGROUND AND OBJECTIVE: Dissection of extracranial arteries that supply the brain is a common cause of ischemic stroke in youngish persons. Yet this disease, with its warning and early symptoms, is inadequately known among the population as well as doctors. This study was undertaken to demonstrate the incidence, severity and sequelae of this condition, important in both routine general and hospital practice, with particular emphasis on early signs and diagnosis. PATIENTS AND METHODS: The data from 33 patients (20 men, 13 women, average age 42 [21-72] years) who during one year had been treated in the authors' hospital for carotid (n = 23) or vertebral (n = 10) artery dissection were analysed. RESULTS: The admission diagnosis of dissection, based on the history and ultrasound findings was in almost all cases confirmed by magnetic resonance imaging (wall haematoma), magnetic resonance angiograhy, computed tomography-angiography or conventional angiography. Typical warning and early symptoms such as whiplash sensation unilateral pain in the throat, neck and head or Horner's syndrome were elicited in nearly 50% of patients, while known causes such as trauma or connective tissue disease were confirmed in only 27%. Neurological deficits of ischemic infarction, some of them severe, persisted in two-thirds of patients, brain death occurred in one. CONCLUSIONS: Dissection of carotid or vertebral arteries is a statistically and medically relevant cause of stroke in youngish persons that can be diagnosed by attention to typical warning and early symptoms and the performance of noninvasive tests. The often life-threatening sequelae of possible cerebral ischemia can be diagnosed and even averted by early recognition of the cause.

Acute Disease↗

[Systemic thrombolytic therapy with rt-PA in acute medial territory infarct. Experiences in routine clinical practice].

BACKGROUND AND PURPOSE: Only a few clinical reports about the routine use of intravenous rt-PA for the treatment of acute ischemic stroke have been published. Wether the perfusion of the extracranial parts of the internal carotid artery influences the outcome of the patients is still unknown, because the two major studies about systemic thrombolytic therapy with rt-PA in stroke (ECASS and NINDS) did not formally assess the status of the extracranial vessels. METHODS: 56 Patients were treated with intravenous rt-PA within 6 h of acute ischemic stroke between January 1995 and May 1998. Before and within 24 h after the thrombolytic therapy usually a neurovascular diagnostic with extra- und transcranial Doppler-ultrasound or CT-angiography was performed. Occlusions of the intracranial parts of the internal carotid artery (Carotid-T) were excluded from thrombolytic therapy. The outcome was assessed using the Rankin-scale at least 3 month after the therapy. RESULTS: The average time from stroke onset to administration of treatment was 3.7 h.A parenchymal hemorrhage with clinical deterioration was found in four patients (7.1%). Eight patients died until the follow-up (14.3%), four within 14 days. 39 patients showed a clinical improvement. Outcome and recanalization rate of the medial cerebral artery was not influenced by stenoses or occlusions of the extracranial internal carotid artery. CONCLUSIONS: Routine intravenous use of rt-PA for acute ischemic stroke shows safety comparable to the results of the NINDS study even in 6 h time window. The outcome and recanalization rate depends not on the perfusion of the extracranial parts of the internal carotid artery.

Acute Disease↗

[Moderate hypothermia for the treatment of malignant middle cerebral artery infarct].

Moderate hypothermia was induced in 30 patients with malignant middle cerebral artery (MCA) territory infarction. Patients were kept at 33 degrees C body-core temperature for 48 to 72 h, and ICP, CPP, and brain temperature were monitored. Outcome at 4 weeks and at 3 months after the stroke as well as side effects of moderate hypothermia were analysed. Mortality of malignant MCA infarction could be reduced from 80% in historical controls, to 43% (13/30) under hypothermia. During hypothermia elevated ICP values could be significantly reduced. Herniation due to a secondary rise of ICP after rewarming was the cause of death in all 13 patients. The most frequent complication of moderate hypothermia was pneumonia in 12 of the 30 patients (40%). Other severe side effects of hypothermia could not be detected. Moderate hypothermia may improve clinical outcome in patients with malignant MCA infarction.

Adolescent↗

External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria. International Association for the Study of Pain.

Recent work in our research consortium has raised internal validity concerns regarding the current IASP criteria for Complex Regional Pain Syndrome (CRPS), suggesting problems with inadequate sensitivity and specificity. The current study explored the external validity of these IASP criteria for CRPS. A standardized evaluation of signs and symptoms of CRPS was conducted by study physicians in 117 patients meeting IASP criteria for CRPS, and 43 patients experiencing neuropathic pain with established non-CRPS etiology (e.g. diabetic neuropathy, post-herpetic neuralgia). Multiple discriminant function analyses were used to test the ability of the IASP diagnostic criteria and decision rules, as well as proposed research modifications of these criteria, to discriminate between CRPS patients and those experiencing non-CRPS neuropathic pain. Current IASP criteria and decision rules (e.g. signs or symptoms of edema, or color changes or sweating changes satisfy criterion 3) discriminated significantly between groups (P < 0.001). However, although sensitivity was quite high (0.98), specificity was poor (0.36), and a positive diagnosis of CRPS was likely to be correct in as few as 40% of cases. Empirically-based research modifications to the criteria, which are more comprehensive and require presence of signs and symptoms, were also tested. These modified criteria were also able to discriminate significantly, between the CRPS and non-CRPS groups (P < 0.001). A decision rule, requiring at least two sign categories and four symptom categories to be positive optimized diagnostic efficiency, with a diagnosis of CRPS likely to be accurate in up to 84% of cases, and a diagnosis of non-CRPS neuropathic pain likely to be accurate in up to 88% of cases. These results indicate that the current IASP criteria for CRPS have inadequate specificity and are likely to lead to overdiagnosis. Proposed modifications to these criteria substantially improve their external validity and merit further evaluation.

Adult↗

Complex regional pain syndrome: are the IASP diagnostic criteria valid and sufficiently comprehensive?

This is a multisite study examining the internal validity and comprehensiveness of the International Association for the Study of Pain (IASP) diagnostic criteria for Complex Regional Pain Syndrome (CRPS). A standardized sign/symptom checklist was used in patient evaluations to obtain data on CRPS-related signs and symptoms in a series of 123 patients meeting IASP criteria for CRPS. Principal components factor analysis (PCA) was used to detect statistical groupings of signs/symptoms (factors). CRPS signs and symptoms grouped together statistically in a manner somewhat different than in current IASP/CRPS criteria. As in current criteria, a separate pain/sensation criterion was supported. However, unlike in current criteria, PCA indicated that vasomotor symptoms form a factor distinct from a sudomotor/edema factor. Changes in range of motion, motor dysfunction, and trophic changes, which are not included in the IASP criteria, formed a distinct fourth factor. Scores on the pain/sensation factor correlated positively with pain duration (P<0. 001), but there was a negative correlation between the sudomotor/edema factor scores and pain duration (P<0.05). The motor/trophic factor predicted positive responses to sympathetic block (P<0.05). These results suggest that the internal validity of the IASP/CRPS criteria could be improved by separating vasomotor signs/symptoms (e.g. temperature and skin color asymmetry) from those reflecting sudomotor dysfunction (e.g. sweating changes) and edema. Results also indicate motor and trophic changes may be an important and distinct component of CRPS which is not currently incorporated in the IASP criteria. An experimental revision of CRPS diagnostic criteria for research purposes is proposed. Implications for diagnostic sensitivity and specificity are discussed.

Adult↗